Sildenafil for DCI

Sponsor

University of Mississippi Medical Center (Other)

Overall Status

Active, not recruiting

CT.gov ID

NCT03028298

Collaborator

(none)

Enrollment

Location

Arms

78.9

Duration (Months)

0.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Each year, approximately 30,000 people in the United States suffer an intra-cranial hemorrhage due to aneurysmal rupture. Of those surviving the initial event, up to 40% will go on to have further neurological injury secondary to stroke (delayed cerebral ischemia) caused by constriction of blood vessels (i.e. vasospasm). Previous studies have shown that the medication sildenafil, given intravenously, improves vasospasm, but has an associated degree of hypotension. The degree of hypotension was well within safety thresholds for these patients.

Sildenafil is a medication that strongly inhibits the protein phosphodiesterase-V (PDE-V). The hypothesis for this study is that oral sildenafil will also improve vasospasm, but does not result in as much hypotension. Specifically, the investigators look to show that comparable doses of oral sildenafil produces the same degree of PDE-V inhibition as an intravenous dose while the degree of hypotension is reduced. Additionally, using measurements of cerebral blood flow regulation acquired using transcranial Doppler ultrasound, the investigators look to show that oral sildenafil produces the same degree of improvement in vasospasm and blood flow regulation.

Condition or Disease	Intervention/Treatment	Phase
Subarachnoid Hemorrhage Cerebral Vasospasm	Drug: Low dose sildenafil citrate Drug: High dose sildenafil citrate	Phase 1

Study Design

Study Type:

Interventional

Anticipated Enrollment :

24 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Patients will be randomly assigned to either low dose sildenafil (20mg oral and 10mg intravenous) or high dose sildenafil (60mg oral and 30 mg intravenous)Patients will be randomly assigned to either low dose sildenafil (20mg oral and 10mg intravenous) or high dose sildenafil (60mg oral and 30 mg intravenous)

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Sildenafil for the Treatment of Delayed Cerebral Ischemia Following Subarachnoid Hemorrhage

Study Start Date :

Dec 1, 2016

Anticipated Primary Completion Date :

Dec 1, 2022

Anticipated Study Completion Date :

Jul 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Low dose sildenafil Twelve patients with cerebral vasospasm following aneurysmal subarachnoid hemorrhage will be assigned to low dose sildenafil citrate and will receive a 20mg oral dose and a subsequent 10mg intravenous dose of sildenafil citrate.	Drug: Low dose sildenafil citrate
Experimental: High dose sildenafil Twelve patients with cerebral vasospasm following aneurysmal subarachnoid hemorrhage will be assigned to high dose sildenafil citrate and will receive a 60mg oral dose and a subsequent 30mg intravenous dose of sildenafil citrate.	Drug: High dose sildenafil citrate

Arm

Intervention/Treatment

Experimental: Low dose sildenafil

Twelve patients with cerebral vasospasm following aneurysmal subarachnoid hemorrhage will be assigned to low dose sildenafil citrate and will receive a 20mg oral dose and a subsequent 10mg intravenous dose of sildenafil citrate.

Drug: Low dose sildenafil citrate

Experimental: High dose sildenafil

Twelve patients with cerebral vasospasm following aneurysmal subarachnoid hemorrhage will be assigned to high dose sildenafil citrate and will receive a 60mg oral dose and a subsequent 30mg intravenous dose of sildenafil citrate.

Drug: High dose sildenafil citrate

Outcome Measures

Primary Outcome Measures

Change from baseline in mean arterial blood pressure [baseline and 2 hours post-dose]
Area under the plasma concentration versus time curve (AUC) of sildenafil [0, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 16, 20, and 24 hours post-dose]

Secondary Outcome Measures

Area under the cerebral spinal fluid concentration versus time curve (AUC) of sildenafil [0, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 16, 20, and 24 hours post-dose]
Change from baseline in cerebral autoregulation [baseline and 2 hours post-dose]

Eligibility Criteria

Criteria

Ages Eligible for Study:

21 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Age >= 21
Onset of symptoms within 72 hours from presentation
Subarachnoid hemorrhage from ruptured cerebral aneurysm
Cerebral vasospasm diagnosed on transcranial doppler, CT angiography, or digital subtraction angiography

Exclusion Criteria:

Pregnancy
Subarachnoid hemorrhage secondary to traumatic or mycotic aneurysm
Pre-ictal sildenafil therapy (last dose within 1 week of presentation)
Contraindications to sildenafil therapy (i.e. use of nitrates, left ventricular outflow obstruction, impaired autonomic blood pressure control)